|
Cell's 'power plant' genes raise vision disorder risk
May 07, 2008Genetic variation in the DNA of mitochondria - the "power plants" of cells - contributes to a person's risk of developing age-related macular degeneration (AMD), Vanderbilt investigators report May 7 in the journal PLoS ONE.
The study is the first to examine the mitochondrial genome for changes associated with AMD, the leading cause of blindness in Caucasians over age 50.
"Most people don't realize that we have two genomes," said lead author Jeff Canter, M.D., M.P.H., an investigator in the Center for Human Genetics Research. "We have the nuclear genome - the "human genome" - that makes the cover of all the magazines, and then we also have this tiny genome in mitochondria in every cell."
Canter teamed with Jonathan Haines, Ph.D., and Paul Sternberg, M.D., experts in AMD genetics and treatment, to examine whether a particular variation in the mitochondrial genome is associated with the disease. The genetic change occurs in about 10 percent of Caucasians, referred to as mitochondrial haplogroup T.
"We suspect that this variant will be one of a small group of important genetic variations that underlie AMD," Canter said. "By knowing this, we have a better chance of predicting accurately who will get the disease."
AMD affects as many as 10 million people in the United States, robbing them of the sharp central vision necessary for everyday activities like reading, driving, watching television, and identifying faces. The toll of the disease is expected to mount as the U.S. population ages.
The genetics of AMD has been a "hot" area lately, Canter said. Haines led a team that identified a variant in the Complement Factor H (CFH) gene as accounting for up to 43 percent of AMD. Variations in ApoE2 and a gene called LOC387715 on chromosome 10 have also been linked to the disease, and Haines and colleagues demonstrated an interaction between the chromosome 10 gene and smoking in raising AMD risk.
The current study also examined variation in these nuclear genes in 280 cases and 280 age-matched controls, and demonstrated that the mitochondrial genome variation was independent of the known nuclear factors.
"We're at the stage where we can use genetic information to predict who is likely to develop AMD well before they actually develop it," said Haines, director of the Center for Human Genetics Research. "Now we can conduct trials of preventive treatments - something's that never been possible before."
Sternberg, G.W. Hale Professor and Chairman of the Vanderbilt Eye Institute, is leading a trial to test preventive measures in AMD.
Variation in the mitochondrial genome reflects human migrations and different environmental exposures. Changes in the mitochondrial DNA can alter the efficiency of energy generation and lead to over-production of "reactive oxygen species" - free radicals that can damage the cell.
"By identifying genetic changes associated with the mitochondria, our results lend additional confirmatory evidence for the role of oxidative stress in AMD," Sternberg said. "This supports study of interventions that attempt to bolster our antioxidant defenses."
"I can see a day when physicians order genotyping on patients at a certain age to determine risk for AMD and put things in place - dietary changes, antioxidants, increased screening - that could prevent the disease," Canter added. "This would be truly personalized medicine."
Canter emphasized that variation in the mitochondrial genome has been linked to a wide variety of diseases including neurodegenerative diseases like Parkinson's and Alzheimer's as well as breast cancer and trauma survival.
"It's important to realize that there's another genome in the mitochondria, and even though there are not many genes there, they're important," Canter said.
Vanderbilt University Medical Center
Canter teamed with Jonathan Haines, Ph.D., and Paul Sternberg, M.D., experts in AMD genetics and treatment, to examine whether a particular variation in the mitochondrial genome is associated with the disease. The genetic change occurs in about 10 percent of Caucasians, referred to as mitochondrial haplogroup T.
"We suspect that this variant will be one of a small group of important genetic variations that underlie AMD," Canter said. "By knowing this, we have a better chance of predicting accurately who will get the disease."
AMD affects as many as 10 million people in the United States, robbing them of the sharp central vision necessary for everyday activities like reading, driving, watching television, and identifying faces. The toll of the disease is expected to mount as the U.S. population ages.
The genetics of AMD has been a "hot" area lately, Canter said. Haines led a team that identified a variant in the Complement Factor H (CFH) gene as accounting for up to 43 percent of AMD. Variations in ApoE2 and a gene called LOC387715 on chromosome 10 have also been linked to the disease, and Haines and colleagues demonstrated an interaction between the chromosome 10 gene and smoking in raising AMD risk.
The current study also examined variation in these nuclear genes in 280 cases and 280 age-matched controls, and demonstrated that the mitochondrial genome variation was independent of the known nuclear factors.
"We're at the stage where we can use genetic information to predict who is likely to develop AMD well before they actually develop it," said Haines, director of the Center for Human Genetics Research. "Now we can conduct trials of preventive treatments - something's that never been possible before."
Sternberg, G.W. Hale Professor and Chairman of the Vanderbilt Eye Institute, is leading a trial to test preventive measures in AMD.
Variation in the mitochondrial genome reflects human migrations and different environmental exposures. Changes in the mitochondrial DNA can alter the efficiency of energy generation and lead to over-production of "reactive oxygen species" - free radicals that can damage the cell.
"By identifying genetic changes associated with the mitochondria, our results lend additional confirmatory evidence for the role of oxidative stress in AMD," Sternberg said. "This supports study of interventions that attempt to bolster our antioxidant defenses."
"I can see a day when physicians order genotyping on patients at a certain age to determine risk for AMD and put things in place - dietary changes, antioxidants, increased screening - that could prevent the disease," Canter added. "This would be truly personalized medicine."
Canter emphasized that variation in the mitochondrial genome has been linked to a wide variety of diseases including neurodegenerative diseases like Parkinson's and Alzheimer's as well as breast cancer and trauma survival.
"It's important to realize that there's another genome in the mitochondria, and even though there are not many genes there, they're important," Canter said.
Vanderbilt University Medical Center
Mitochondrial Genome News and Current Mitochondrial Genome Events RSSWoolly-Mammoth Gene Study Changes Extinction Theory
A large genetic study of the extinct woolly mammoth has revealed that the species was not one large homogenous group, as scientists previously had assumed, and that it did not have much genetic diversity.
Researchers posit new ideas about human migration from Asia to Americas
Questions about human migration from Asia to the Americas have perplexed anthropologists for decades, but as scenarios about the peopling of the New World come and go, the big questions have remained.
Scientists show that mitochondrial DNA variants are linked to risk factors for type 2 diabetes
Today, researchers report for the first time that genetic variants in mitochondria-energy-producing structures harboring DNA that are inherited only from the mother-are directly linked to metabolic markers for type 2 diabetes.
Back to the future: Mastodon extends the time limit on DNA sequencing
In a new paper in the open access journal PLoS Biology, Michael Hofreiter from the Max Planck Institute for Evolutionary Anthropology in Germany, and colleagues from Switzerland and the United States, announce the sequencing of the complete mitochondrial genome of the mastodon (Mammut americanum), a recently extinct relative of the living elephants that diverged about 26 million years ago.
Robust time estimation reconciles views of the antiquity of placental mammals
Despite great progress over the past decade, the evolutionary history of placental mammals remains controversial. While a consensus is emerging on the topology of the evolutionary tree, although with occasional disagreement, divergence times remain uncertain.
Rodent's bizarre traits deepen mystery of genetics, evolution
A shadowy rodent has potential to shed light on human genetics and the mysteries of evolution.
Mitochondrial DNA sequencing tool updated
High-tech laboratory tools, like computers, are often updated publicly as their analytical capabilities expand. In the September issue of the Journal of Molecular Diagnostics, NIH grantees report they have developed a second generation "lab on a silicon chip" called the MitoChip v2.0 that for the first time rapidly and reliably sequences all mitochondrial DNA.
Scientists sequence DNA of woolly mammoth
Experts in ancient DNA from McMaster University (Canada) have teamed up with genome researchers from Penn State University (USA) for the investigation of permafrost bone samples from Siberia.
Nature press release for 13 September issue
[413127] PHENOMENA: STAGGERED CYCLISTS STAY APART (p127) Staging cycling and orienteering races to prevent the competitors forming into packs may be helped by a Brief Communication in this week’s Nature. In races, cyclists in a pack can move faster than those alone, by taking turns to front the pack and sharing the benefits from reduced air resistance. Orienteers can also profit from travelling in packs by sharing map-reading information. But this makes it difficult to compare the true ability of individuals. Graeme Ackland and David Butler of the University of Edinburgh, UK, constructed a model to predict race conditions that precipitate pack formation. If 13% of competitors can see a
More Mitochondrial Genome News Articles
| © 2008 BrightSurf.com |